Evaluating steroid-free clinical remission of filgotinib and azathioprine in patients with steroid-dependent ulcerative colitis - an open label randomized controlled trial (EVOLUTION)
EVOLUTION trial
Kobayashi Taku
Kitasato University Kitasato Institute Hospital
5-9-1,Shirokane,Minato-ku,Tokyo,108-8642,Japan
+81-3-3444-6161
drkobataku@gmail.com
Watanabe Yuki
Kitasato University Kitasato Institute Hospital
5-9-1,Shirokane,Minato-ku,Tokyo,108-8642,Japan
+81-3-3444-6161
yuki-w@insti.kitasato-u.ac.jp
Recruiting
Nov. 20, 2024
April. 30, 2025
134
Interventional
randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
1) Must understand and sign an ICF obtained before any study procedures are performed.
2) Male or female between 18 to under 65 years of age inclusive, based on the date of the screening visit.
3) Diagnosis of UC for at least 3 months before the screening visit with involvement of at least 15 cm from the anal verge.
4) Subjects with moderately to severely active UC who undergo an endoscopy during screening and have an endoscopic subscore of greater than or equal to 2,and a total score of greater than or equal to 4, as determined by central review.
5) Patients who have used oral steroids (initial dose of prednisolone 30 mg/day or budesonide greater than or equal to 9 mg/day) and experienced response within 2 year before informed consent.
6 Patients who experience a relapse during oral steroid tapering or within two years after discontinuation.
7) The dose of steroids has been less than or equal to 10 mg/day for at least 14 days before randomization (subjects on budesonide must be off the drug). Subjects may be off steroids.
8) Subjects must not have active tuberculosis or untreated latent tuberculosis.
9) Subjects must not have severe hepatic impairment, classified as Child-Pugh class C.
10) Laboratory parameters:
a) eGFR greater than or equal to 60mL/min/1.73 m2
b) Hemoglobin greater than or equal to 8.0 g/dL
c) Absolute neutrophil count (ANC) greater than or equal to 1.0 x 10 9/L (1000/mm3)
d) White blood cell count (WBC) greater than 3000/mm3
e) Absolute lymphocyte count greater than or equal to 500/mm3
11) For subjects on oral 5-aminosalicylic acid (5-ASA), the dose must have been stable for at least 2 weeks prior to randomization. The dose must remain stable (Subjects on these treatments must be willing to remain on a stable dose for the specified duration) for the first 10 weeks after randomization.
12) Patients willing to abstain from receiving live or attenuated vaccines throughout the study and for 12 weeks after the last dose.
1) Pregnant or lactating women
2) Those who wish to become pregnant within the next year
3) Women who are planning to donate eggs or collect eggs for the purpose of fertilization for the present or future during this study period or within 35 days after the last dose of the clinical study drug
4) Men who are not willing to refrain from sperm donation for at least 90 days after the last dose of the clinical study drug
5) Known hypersensitivity to the excipients of the FIL/AZA, its metabolites, or formulation
6) Patients with severe acute UC as defined by the following criteria
a) Six or more bloody stools per day and one or more of the following:
i) Body temperature 38.0 degrees Celsius or higher
ii) Pulse rate > 90 beats/min
7) Patients with a history of the following UC treatments
a) TNF Alpha inhibitors (e.g. infliximab, adalimumab, golimab, or biosimilars)
b) IL-12/23 inhibitors (e.g. ustekinumab, mirikizumab)
c) Cell trafficking regulators (e.g., vedolizumab, ozanimod, carotegrast methyl)
*The use of carotegrast methyl is allowed only if it occurred prior to the most recent start date of steroid administration.
d) Janus kinase inhibitors (e.g., tofacitinib, FIL, upadacitinib)
e) Calcineurin inhibitors (e.g., tacrolimus, cyclosporine)
8) Patients with a history or current use of immunomodulatory agents, including but not limited to AZA, 6-MP, or MTX
9) Patients with the NUDT15 gene R139C polymorphism (Cys/Cys, Arg/Cys, or Cys/His)
10) Patients with a history of greater than or equal to 3 cycles of oral steroids for the treatment of UC
11) Before screening, patients who have been continuously using oral steroids for more than 6 months
12) Patients with a history of severe adverse events from steroid therapy
13) Patients who underwent major surgery or trauma within 30 days prior to screening
14) Patients with a history of surgical treatment for UC (e.g., total colectomy, subtotal colectomy, partial colectomy, hemicolectomy, ileostomy, colostomy) or who may require surgery during the clinical study period
15) Patients receiving nutritional therapy
16) Patients with a history of cytapheresis within 30 days prior to screening
17) Patients using prohibited concomitant drugs
18) Patients with clinically significant active infections
19) Other patients who the principal investigator (subinvestigator) deems inappropriate to administer the clinical study drug.
18age old over
65age old not
Both
ulcerative colitis
FIL group : Filgotinib (trade name : Jyseleca Registered) 200 mg administered orally once daily for 52 weeks
AZA and corticosteroid group : Azathioprine (trade name : Azanin Registered or Imuran Registered) administered orally for 52 weeks. Steroids were used in combination until the 12th week of treatment.
Proportion of patients who achieved steroid-free EBS remission at Week 52.
-Proportion of subjects with endoscopic remission at Week52
-Proportion of subjects achieving endoscopic response at Week52
-Proportion of subjects achieving Geboes histological remission at Week52
-Proportion of subjects with HEMI at Week52
-Proportion of subjects achieving HEMR at Week52
<Other secondary endpoints>
-Incidence of AEs in the FIL and AZA plus corticosteroid groups up to Week52
-Percentage of discontinuation of FIL and AZA due to adverse events up to Week52
-Proportion of subjects achieving daily PRO-2 score of 0 or 1(Rectal bleeding subscore = 0,stool frequency subscore = 0,1) through Week2
-Proportion of subjects achieving a PRO-2 score of 0 or 1(Rectal bleeding subscore = 0,stool frequency subscore = 0,1) at Week12
-Proportion of subjects achieving a PRO-2 score of 0 or 1(Rectal bleeding subscore = 0,stool frequency subscore = 0,1) at Week52
-Change from baseline in daily urgency NRS by Week2
-Change from baseline in urgency NRS at Weeks 12 and52
-Change from baseline in FACIT-F at Week52
-WPAI:Change from Baseline in UC at Week52
-Change from baseline in IBDQ at Week52
-Change from baseline in UC-PRO/SS at Week52
